Stent coating apparatus

ABSTRACT

An apparatus for coating stent is disclosed. The apparatus can be used to coat multiple stents or a large number of stents simultaneously. The apparatus includes a chamber that can be rotated or tumbled during the application of a coating substance to the stents.

CROSS REFERENCE

[0001] This is a continuation of application Ser. No. 09/966,420, filedon Sep. 27, 2001.

BACKGROUND

[0002] This invention relates to a stent coating apparatus. Percutaneoustransluminal coronary angioplasty (PTCA) is a procedure for treatingheart disease. A catheter assembly having a balloon portion isintroduced percutaneously into the cardiovascular system of a patientvia the brachial or femoral artery. The catheter assembly is advancedthrough the coronary vasculature until the balloon portion is positionedacross the occlusive lesion. Once in position across the lesion, theballoon is inflated to a predetermined size to radially press againstthe atherosclerotic plaque of the lesion for remodeling of the vesselwall. The balloon is then deflated to a smaller profile to allow thecatheter to be withdrawn from the patient's vasculature.

[0003] A problem associated with the above procedure includes formationof intimal flaps or torn arterial linings which can collapse and occludethe conduit after the balloon is deflated. Vasospasms and recoil of thevessel wall also threaten vessel closure. Moreover, thrombosis andrestenosis of the artery may develop over several months after theprocedure, which may require another angioplasty procedure or a surgicalby-pass operation. To reduce the partial or total occlusion of theartery by the collapse of arterial lining and to reduce the chance ofthe development of thrombosis and restenosis, a stent is implanted inthe lumen to maintain the vascular patency.

[0004]FIG. 1 illustrates a conventional stent 10 formed from a pluralityof struts 12. The plurality of struts 12 are radially expandable andinterconnected by connecting elements 14 that are disposed betweenadjacent struts 12, leaving lateral openings or gaps 16 between adjacentstruts 12. Struts 12 and connecting elements 14 define a tubular stentbody having an outer, tissue-contacting surface and an inner surface.

[0005] Stents may be used not only as a mechanical intervention but alsoas a vehicle for providing biological therapy. As a mechanicalintervention, stents may act as scaffoldings, functioning to physicallyhold open and, if desired, to expand the wall of the passageway.Typically stents are capable of being compressed, so that they can beinserted through small cavities via catheters, and then expanded to alarger diameter once they are at the desired location. Examples inpatent literature disclosing stents which have been applied in PTCAprocedures include stents illustrated in U.S. Pat. No. 4,733,665 issuedto Palmaz, U.S. Pat. No. 4,800,882 issued to Gianturco, and U.S. Pat.No. 4,886,062 issued to Wiktor. Mechanical intervention via stents hasreduced the rate of restenosis as compared to balloon angioplasty;restenosis, however, is still a significant clinical problem. Whenrestenosis does occur in the stented segment, its treatment can bechallenging, as clinical options are more limited as compared to lesionsthat were treated solely with a balloon.

[0006] Biological therapy can be achieved by medicating the stents.Medicated stents provide for the local administration of a therapeuticsubstance at the diseased site. In order to provide an efficaciousconcentration to the treated site, systemic administration of suchmedication often produces adverse or toxic side effects for the patient.Local delivery is a preferred method of treatment in that smaller totallevels of medication are administered in comparison to systemic dosages,but are concentrated at a specific site. Local delivery thus producesfewer side effects and achieves more favorable results.

[0007] Although stents work well mechanically, the chronic issues ofrestenosis and, to a lesser extent, stent thrombosis remain. Theseevents are affected by, and made worse, by mechanical aspects of thestent such as the degree of injury and disturbance of hemodynamics. Tothe extent that the mechanical functionality of stents has beenoptimized, it has been postulated that continued improvements could bemade by pharmacological therapies. Many systemic therapies have beentried. A challenge is maintaining the necessary concentration of drug atthe lesion site for the necessary period of time. This can be done viabrute force methods using oral or intravenous administration but theissues of systemic toxicity and side effects arise. Therefore, apreferred route may be achieved by local delivery of drug from the stentitself. Stents are composed of struts that are typically 50-150 micronswide. Being made of metal, plain stents are not useful for drugdelivery. Therefore, a coating, usually of a polymer, is applied toserve as a drug reservoir.

[0008] Slotted tube stents are made by laser cutting a solid metalhypotube. Leading stent manufacturers can produce thousands of stentsper day. Consequently, the drug coating process, which is added on tothe existing stent manufacturing process, needs to be rapid andreproducible. Stents are difficult to coat evenly due to their intricategeometry and small size. Conventional coating techniques fill in thespaces between struts creating webbing and bridging. A versatile methodof stent coating is by a spray process that avoids webbing by theapplication of small droplets.

[0009] In order to coat a stent, it typically must be held in somemanner. This allows it to be positioned and moved under a spray nozzlein a controlled and repeatable manner. However, holding a stent requiresmaking contact with it. At these contact points, the liquid coating canweb, accumulate or wick. After drying, this leads to thick coatingdeposits at the contacts between the stent and the fixture. Thesedeposits can also attach the stent to the holding fixture, which createstearing and bare spots when the two are eventually separated. It isdesirable that the stent be completely coated on all surfaces with nosignificant bare spots. It is also desirable that there be nosignificant defects associated with the fixturing. It is furtherdesirable that a coating process is capable of allowing the coating of alarge amount or number of stents at one time.

SUMMARY OF THE INVENTION

[0010] A large-scale stent coating apparatus is disclosed, comprising achamber to hold a multitude of stents, the chamber being configured toagitate so as to shake the stents within the chamber; and an applicatorfor depositing a coating substance into the chamber for coating thestents.

[0011] In some embodiments, the apparatus additionally includes a systemfor applying a gas into the chamber.

[0012] A large-scale stent coating apparatus is disclosed, comprising achamber for holding a large number of stents, the chamber beingconfigured to shake so as to tumble the stents by the shaking motion ofthe chamber; an applicator for depositing a coating substance into thechamber for coating the stents.

[0013] A large-scale stent coating apparatus is disclosed, comprising achamber configured to hold a multitude of stents, the chamber beingconfigured to rotate about an axis that is parallel to the horizontalplane so as to tumble the stents in the chamber; and an applicator fordepositing a coating substance into the chamber for coating the stents.

BRIEF DESCRIPTION OF THE DRAWINGS

[0014]FIG. 1 illustrates a conventional stent; and

[0015]FIG. 2 is a schematic flow diagram illustrating a process forcoating an implantable device in accordance with an embodiment of thepresent invention.

DETAILED DESCRIPTION

[0016]FIG. 2 is a schematic flow diagram illustrating a general overviewof a process 200 for coating an implantable device, such as a stent, inaccordance with an embodiment of the present invention. At least onestent 202 is deposited in a pan 204 (see A of FIG. 2).

[0017] The pan 204 is agitated to tumble the stent(s) 202 in the pan 204(see B of FIG. 2). Agitation of the pan 204 may be achieved utilizing avariety of modes including, but not limited to, shaking of the pan 204to tumble the stent(s) 202 therein. As illustrated in FIG. 2, in oneembodiment, agitation of the pan 204 may be achieved by tilting the pan204 with respect to a horizontal plane 206 such that an axis 208 of thepan 204 extends at an acute angle (e.g., extending at an angle between 0degrees and 90 degrees) to the horizontal plane 206. The pan 204 can berotated about the axis 208 to tumble the stent(s) 202 in the pan 204. Asan option, the rotating axis 208 may extend at about 45 degrees withrespect to the horizontal plane 206. In one embodiment, the pan 204 maybe rotated between about 5 revolutions per minute (rpm) and about 400rpm and in a preferred embodiment between about 10 rpm and about 200rpm.

[0018] Continuing the process 200, a coating substance is introduced tocoat the tumbling stent(s) 202. In one embodiment, the coating substance210 may be sprayed into the pan 204 to coat the tumbling stent(s) 202with the coating substance (see C of FIG. 2). Because of the continuoustumbling motion, the spray coating solution is divided equally over thestents 202. In one embodiment, the coating substance may comprise apolymer dissolved in a fluid and, optionally, an active agent addedthereto. The actual spray time chosen may depend on various factors suchas, for example, the equipment used, the number of stents beingdeposited in the pan 204, and the volatility of the solvent.

[0019] As a further option, gaseous composition 212 may be directed overthe tumbling stent(s) 202 to aid in the drying of the coating substanceon the stent(s) 202. In the embodiment illustrated in FIG. 2, thegaseous compound 212 may be blown into the rotating pan 204 to aiddrying of the coating substance 210 on the tumbling stent(s) 202 (see Dof FIG. 2). In one such embodiment, the gaseous composition 212 maycomprise air. As another option, the gaseous composition 212 may have atemperature between about 15° C. and about 200° C.

[0020] It should further be noted that one or more subsequent coatingsubstances may also be sequentially introduced to the tumblingimplantable device to apply one or more further coatings on theimplantable device.

[0021] Embodiments of the disclosed process may be utilized to coat oneor more stents (especially large numbers of stents)—including drugdelivery stents. The process may be utilized used to apply primers, drugcontaining layers, and/or topcoats. The significance of this process istwo-fold: this process simplifies the spray process and increases itsreproducibility by virtue of being a simpler process. Additionally,since the stent is not contacted continuously at any one point, theissue of end ring defects should be reduced or essentially eliminated.It should also be noted that embodiments of the disclosed process maybeused on any drug eluting stent. Such coatings can be used on balloonexpandable or self-expanding stents. The stent may be utilized in anypart of the vasculature including neurological, carotid, coronary,renal, aortic, iliac, femoral, or other peripheral vasculature. Theremay also be no limitations on stent length, diameter, strut thickness,strut pattern, or stent material.

[0022] Implantable Devices

[0023] While the process detailed herein is often described withreference to coating a stent, it should be understood that the device orprosthesis coated in accordance with the embodiments of the presentinvention may be any suitable medical substrate that can be implanted ina human or veterinary patient. Examples of such implantable devicesinclude stent-grafts, grafts (e.g., aortic grafts), artificial heartvalves, cerebrospinal fluid shunts, anastomosis devices (e.g., AXIUSCoronary Shunt available from Guidant Corporation), pacemakerelectrodes, and endocardial leads (e.g., FINELINE and ENDOTAK, availablefrom Guidant Corporation). The underlying structure of the device can beof virtually any design. The device can be made of a metallic materialor an alloy such as, but not limited to, cobalt chromium alloy(ELGILOY), stainless steel (316L), “MP35N,” “MP20N,” ELASTINITE(Nitinol), tantalum, nickel-titanium alloy, platinum-iridium alloy,gold, magnesium, or combinations thereof. “MP35N” and “MP20N” are tradenames for alloys of cobalt, nickel, chromium and molybdenum availablefrom standard Press Steel Co., Jenkintown, Pa. “MP35N” consists of 35%cobalt, 35% nickel, 20% chromium, and 10% molybdenum. “MP20N” consistsof 50% cobalt, 20% nickel, 20% chromium, and 10% molybdenum. Devicesmade from bioabsorbable or biostable polymers could also be used withthe embodiments of the present invention. A polymeric implantable deviceshould be compatible with the composition. The ethylene vinyl alcoholcopolymer, however, adheres very well to metallic materials, morespecifically to stainless steel.

[0024] Coating Substance

[0025] In an embodiment of the present invention, the coating substancemay include a polymer dissolved in a fluid and optionally, an activeagent added thereto. As a further option, the coating substance mayinclude radiopaque elements, or radioactive isotopes.

[0026] Representative examples of polymers that can be used to coat astent include ethylene vinyl alcohol copolymer (commonly known by thegeneric name EVOH or by the trade name EVAL), poly(hydroxyvalerate);poly(L-lactic acid); polycaprolactone; poly(lactide-co-glycolide);poly(hydroxybutyrate); poly(hydroxybutyrate-co-valerate); polydioxanone;polyorthoester; polyanhydride; poly(glycolic acid); poly(D,L-lacticacid); poly(glycolic acid-co-trimethylene carbonate); polyphosphoester;polyphosphoester urethane; poly(amino acids); cyanoacrylates;poly(trimethylene carbonate); poly(iminocarbonate); copoly(ether-esters)(e.g. PEO/PLA); polyalkylene oxalates; polyphosphazenes; biomolecules,such as fibrin, fibrinogen, cellulose, starch, collagen and hyaluronicacid; polyurethanes; silicones; polyesters; polyolefins; polyisobutyleneand ethylene-alphaolefin copolymers; acrylic polymers and copolymers;vinyl halide polymers and copolymers, such as polyvinyl chloride;polyvinyl ethers, such as polyvinyl methyl ether; polyvinylidenehalides, such as polyvinylidene fluoride and polyvinylidene chloride;polyacrylonitrile; polyvinyl ketones; polyvinyl aromatics, such aspolystyrene; polyvinyl esters, such as polyvinyl acetate; copolymers ofvinyl monomers with each other and olefins, such as ethylene-methylmethacrylate copolymers, acrylonitrile-styrene copolymers, ABS resins,and ethylene-vinyl acetate copolymers; polyamides, such as Nylon 66 andpolycaprolactam; alkyd resins; polycarbonates; polyoxymethylenes;polyimides; polyethers; epoxy resins; polyurethanes; rayon;rayon-triacetate; cellulose; cellulose acetate; cellulose butyrate;cellulose acetate butyrate; cellophane; cellulose nitrate; cellulosepropionate; cellulose ethers; and carboxymethyl cellulose.

[0027] In an embodiment of the present invention, the fluid in which thepolymer is dissolved may comprise a solvent which may be defined as aliquid substance or composition that is compatible with the polymer andis capable of dissolving the polymer at the concentration desired in thecomposition. Examples of solvents include, but are not limited to,dimethylsulfoxide (DMSO), chloroform, acetone, water (buffered saline),xylene, methanol, ethanol, 1-propanol, tetrahydrofuran, 1-butanone,dimethylformamide, dimethylacetamide, cyclohexanone, ethyl acetate,methylethylketone, propylene glycol monomethylether, isopropanol,isopropanol admixed with water, N-methyl pyrrolidinone, toluene, andcombinations thereof.

[0028] The embodiments of the composition may be prepared byconventional methods wherein all components are combined, then blended.For example, in an illustrative embodiment, a predetermined amount of anethylene vinyl alcohol copolymer may be added to a predetermined amountof dimethyl acetamide (DMAC or DMAc). If necessary, heating, stirringand/or mixing can be employed to effect dissolution of the copolymerinto the solvent—for example in an 80° C. water bath for one to twohours.

[0029] Active Agent

[0030] The active agent may be in true solution or saturated in theblended composition. If the active agent is not completely soluble inthe composition, operations including mixing, stirring, and/or agitationcan be employed to effect homogeneity of the residues. The active agentmay be added in fine particles. The mixing of the active agent can beconducted at ambient pressure and at room temperature such thatsupersaturating the active ingredient is not desired. The active agentcan be for inhibiting the activity of vascular smooth muscle cells. Morespecifically, the active agent can be aimed at inhibiting abnormal orinappropriate migration and/or proliferation of smooth muscle cells forthe inhibition of restenosis. The active agent can also include anysubstance capable of exerting a therapeutic or prophylactic effect inthe practice of the present invention. For example, the agent can be forenhancing wound healing in a vascular site or improving the structuraland elastic properties of the vascular site. Examples of agents includeantiproliferative substances such as actinomycin D, or derivatives andanalogs thereof (manufactured by Sigma-Aldrich 1001 West Saint PaulAvenue, Milwaukee, Wis. 53233; or COSMEGEN available from Merck).Synonyms of actinomycin D include dactinomycin, actinomycin IV,actinomycin I₁, actinomycin X₁, and actinomycin Cl. The active agent canalso fall under the genus of antineoplastic, anti-inflammatory,antiplatelet, anticoagulant, antifibrin, antithrombin, antimitotic,antibiotic, antiallergic and antioxidant substances. Examples of suchantineoplastics and/or antimitotics include paclitaxel (e.g. TAXOL® byBristol-Myers Squibb Co., Stamford, Conn.), docetaxel (e.g. Taxotere®,from Aventis S. A., Frankfurt, Germany) methotrexate, azathioprine,vincristine, vinblastine, fluorouracil, doxorubicin hydrochloride (e.g.Adriamycin from Pharmacia & Upjohn, Peapack N.J.), and mitomycin (e.g.Mutamycin® from Bristol-Myers Squibb Co., Stamford, Conn.). Examples ofsuch antiplatelets, anticoagulants, antifibrin, and antithrombinsinclude sodium heparin, low molecular weight heparins, heparinoids,hirudin, argatroban, forskolin, vapiprost, prostacyclin and prostacyclinanalogues, dextran, D-phe-pro-arg-chloromethylketone (syntheticantithrombin), dipyridamole, glycoprotein IIb/IIIa platelet membranereceptor antagonist antibody, recombinant hirudin, and thrombininhibitors such as Angiomax a (Biogen, Inc., Cambridge, Mass.). Examplesof such cytostatic or antiproliferative agents include angiopeptin,angiotensin converting enzyme inhibitors such as captopril (e.g.Capoten® and Capozide® from Bristol-Myers Squibb Co., Stamford, Conn.),cilazapril or lisinopril (e.g. Prinivil® and Prinzide® from Merck & Co.,Inc., Whitehouse Station, N.J.); calcium channel blockers (such asnifedipine), colchicine, fibroblast growth factor (FGF) antagonists,fish oil (omega 3-fatty acid), histamine antagonists, lovastatin (aninhibitor of HMG-CoA reductase, a cholesterol lowering drug, brand nameMevacor® from Merck & Co., Inc., Whitehouse Station, N.J.), monoclonalantibodies (such as those specific for Platelet-Derived Growth Factor(PDGF) receptors), nitroprusside, phosphodiesterase inhibitors,prostaglandin inhibitors, suramin, serotonin blockers, steroids,thioprotease inhibitors, triazolopyrimidine (a PDGF antagonist), andnitric oxide. An example of an antiallergic agent is permirolastpotassium. Other therapeutic substances or agents which may beappropriate include alpha-interferon, genetically engineered epithelialcells, rapamycin and dexamethasone.

[0031] Examples of radiopaque elements include, but are not limited to,gold, tantalum, and platinum. An example of a radioactive isotope isP³². Sufficient amounts of such substances may be dispersed in thecomposition such that the substances are not present in the compositionas agglomerates or flocs.

[0032] The dosage or concentration of the active agent required toproduce a favorable therapeutic effect should be less than the level atwhich the active agent produces toxic effects and greater than the levelat which non-therapeutic results are obtained. The dosage orconcentration of the active agent required to inhibit the desiredcellular activity of the vascular region can depend upon factors such asthe particular circumstances of the patient; the nature of the trauma;the nature of the therapy desired; the time over which the ingredientadministered resides at the vascular site; and if other therapeuticagents are employed, the nature and type of the substance or combinationof substances. Therapeutic effective dosages can be determinedempirically, for example by infusing vessels from suitable animal modelsystems and using immunohistochemical, fluorescent or electronmicroscopy methods to detect the agent and its effects, or by conductingsuitable in vitro studies. Standard pharmacological test procedures todetermine dosages are understood by one of ordinary skill in the art.

[0033] Application Process

[0034] In accordance with an embodiment of the present invention, thecoating substance may be sprayed on to the stents utilizing a sprayapparatus, such as, for example, an EFD 780S spray device with VALVEMATE7040 control system (manufactured by EFD Inc., East Providence, R.I.).EFD spray device is an air-assisted external mixing atomizer. Thecomposition is atomized into small droplets by air and uniformly appliedto the stent surface. The atomization pressure can be maintained at arange of about 5 to 20 psi. The droplet size depends on such factors asviscosity of the solution, surface tension of the solvent, and atomizingpressure. Other types of spray applicators, including air-assistedinternal mixing atomizers and ultrasonic applicators can also be usedfor the application of the composition.

[0035] The flow rate of the solution from the spray nozzle can be fromabout 0.01 mg/second to about 1.0 mg/second, for example about 0.1mg/second. As an option, multiple repetitions for applying thecomposition can be performed, wherein each repetition is about 1 secondto about 10 seconds, for example about 5 seconds, in duration. Theamount of coating applied by each repetition can be about 0.1micrograms/cm (of stent surface) to about 10 micrograms/cm, for exampleless than about 2 micrograms/cm per 5 second spray.

[0036] Each repetition can be followed by removal of a significantamount of the solvent(s). The removal of the solvent(s) can be performedfollowing a waiting period of about 0.1 second to about 5 seconds afterthe application of the coating composition so as to allow the liquidsufficient time to flow and spread over the stent surface before thesolvent(s) is removed to form a coating. The waiting period isparticularly suitable if the coating composition contains a volatilesolvent, such as solvents having boiling points >130° C. at ambientpressure, since such solvents are typically removed quickly.

[0037] Removal of the solvent(s) can be induced by the application of agas or air. The application of a warm gas between each repetitionprevents coating defects and minimizes interaction between the activeagent and the solvent. Any suitable gas can be employed, examples ofwhich include air or nitrogen. The temperature of the gas can be fromabout 15° C. to about 200° C. In one embodiment, for temperature stabledrugs, the drying air temperature can be from ambient temperature up toabout 100° C. and for drugs that are temperature sensitive, thetemperature may be from ambient temperature up to about 50° C. The flowspeed of the gas can be from about 0.5 feet³/second (0.01meters³/second) to about 50 feet³/second (1.42 meters³/second), morenarrowly about 2.5 feet³/second (0.07 meters³/second) to about 15feet³/second (0.43 meters³/second). The gas can be applied for about 1second to about 100 seconds, more narrowly for about 2 seconds to about20 seconds. By way of example, warm gas applications can be performed ata temperature of about 60° C., at a flow speed of about 10 feet³/second,and for about 10 seconds.

[0038] In one embodiment, the stent can be warmed to a temperature offrom about 35° C. to about 80° C. prior to the application of thecoating composition so as to facilitate faster removal of thesolvent(s). The particular temperature selected depends, at least inpart, on the particular active agent employed in the coatingcomposition. By way of example, pre-heating of the stent prior toapplying a composition containing actinomycin D should be performed at atemperature not greater than about 55° C. Pre-heating is particularlysuitable for embodiments in which the solvent(s) employed in the coatingcomposition has a high boiling point, i.e., volatile solvents havingboiling points of, for example, >130° C. at ambient pressure (e.g.,dimethylsulfoxide (DMSO), dimethylformamide (DMF), and dimethylacetamide(DMAC)).

[0039] Any suitable number of repetitions of applying the compositionfollowed by removing the solvent(s) can be performed to form a coatingof a desired thickness or weight. In embodiments in which the coatingcomposition contains a volatile solvent, a waiting period of from about0.1 second to about 20 seconds can be employed between solvent removalof one repetition and composition application of the subsequentrepetition so as to ensure that the wetting rate of the coatingcomposition is slower than the evaporation rate of the solvent withinthe composition, thereby promoting coating uniformity.

[0040] Coating Layers

[0041] To form an optional primer layer on the surface of the device, anembodiment of the composition free from any active agents is applied tothe surface of the device. For the thermoplastic polymers, thecomposition could be exposed to a heat treatment at a temperature rangeof greater than about the glass transition temperature and less thanabout the melting temperature of the copolymer. The device should beexposed to the heat treatment for any suitable duration of time (e.g.,30 minutes) which would allow for the formation of the primer layer onthe surface of the device and allows for the evaporation of the solvent.The primer can be used for increasing the retention of a reservoircoating containing the active agent on the surface of the device,particularly metallic surfaces such as stainless steel. The primer canact as an intermediary adhesive tie layer between the surface of thedevice and the coating carrying the active agent—which, in effect,allows for the quantity of the active agent to be increased in thereservoir coating.

[0042] For the formation of the reservoir coating containing an activeagent, an embodiment of the composition containing an active agent orcombination of agents is applied to the device. If a primer layer isemployed, the application should be performed subsequent to the dryingof the primer layer.

[0043] An optional topcoat can be formed over the reservoir coatingcontaining the active agents. An embodiment of the composition, freefrom any active agents, can be applied to the reservoir regionsubsequent to the drying of the reservoir region. The solvent is thenallowed to evaporate, for example, by exposure to a selectedtemperature, to form the rate-limiting diffusion barrier.

[0044] For the reservoir coating containing the active agent and theoptional top coat, a final heat treatment could be conducted to removeessentially all of the solvent(s) from the composition on the stent. Theheat treatment can be conducted at about 30° C. to about 200° C. forabout 15 minutes to about 16 hours, more narrowly at about 50° C. toabout 100° C. for about 1 hour to about 4 hours. By way of example, theheat treatment can be conducted at about 75° C. for 1 hour. Thetemperature of exposure should not adversely affect the characteristicsof the active agent or of the coating. The heating can be conducted inan anhydrous atmosphere and at ambient pressure. The heating can,alternatively, be conducted under a vacuum condition. It is understoodthat essentially all of the solvent(s) will be removed from thecomposition but traces or residues can remain blended in the coating.

[0045] Method of Use

[0046] A stent having the above-described coating is useful for avariety of medical procedures, including, by way of example, treatmentof obstructions caused by tumors in bile ducts, esophagus,trachea/bronchi and other biological passageways. A stent having theabove-described coating is particularly useful for treating occludedregions of blood vessels caused abnormal or inappropriate migration andproliferation of smooth muscle cells, thrombosis, and restenosis. Stentsmay be placed in a wide array of blood vessels, both arteries and veins.Representative examples of sites include the iliac, renal, and coronaryarteries.

[0047] Briefly, an angiogram is first performed to determine theappropriate positioning for stent therapy. Angiogram is typicallyaccomplished by injecting a radiopaque contrasting agent through acatheter inserted into an artery or vein as an x-ray is taken. Aguidewire is then advanced through the lesion or proposed site oftreatment. Over the guidewire is passed a delivery catheter which allowsa stent in its collapsed configuration to be inserted into thepassageway. The delivery catheter is inserted either percutaneously orby surgery into the femoral artery, brachial artery, femoral vein, orbrachial vein, and advanced into the appropriate blood vessel bysteering the catheter through the vascular system under fluoroscopicguidance. A stent having the above described coating may then beexpanded at the desired area of treatment. A post insertion angiogrammay also be utilized to confirm appropriate positioning.

[0048] While particular embodiments of the present invention have beenshown and described, it will be obvious to those skilled in the art thatchanges and modifications can be made without departing from thisinvention in its broader aspects and, therefore, the appended claims areto encompass within their scope all such changes and modifications asfall within the true spirit and scope of this invention.

What is claimed is:
 1. A large-scale stent coating apparatus, comprisinga chamber to hold a multitude of stents, the chamber being configured toagitate so as to shake the stents within the chamber; and an applicatorfor depositing a coating substance into the chamber for coating thestents.
 2. The apparatus of claim 1, additionally comprising means forapplying a gas into the chamber.
 3. The apparatus of claim 1,additionally comprising means for drying the coating applied to thestents within the chamber.
 4. The apparatus of claim 1, additionallycomprising means for applying a gas at a temperature of 15 deg. C to 200deg. C into the chamber.
 5. A large-scale stent coating apparatus,comprising a chamber for holding a large number of stents, the chamberbeing configured to shake so as to tumble the stents by the shakingmotion of the chamber; an applicator for depositing a coating substanceinto the chamber for coating the stents.
 6. The apparatus of claim 5,additionally comprising a nozzle for applying a gas into the chamber. 7.A large-scale stent coating apparatus, comprising a chamber configuredto hold a multitude of stents, the chamber being configured to rotateabout an axis that is parallel to the horizontal plane so as to tumblethe stents in the chamber; and an applicator for depositing a coatingsubstance into the chamber for coating the stents.
 8. The apparatus ofclaim 7, wherein the chamber is configured to rotate between 5 to 400rpm.
 9. The apparatus of claim 7, additionally including means forblowing a gas into the chamber.